The present invention relates to a microchip processing apparatus for performing analysis by a microchip electrophoresis method or micro liquid chromatography, or the like, in fields such as chemistry and life science, and a device for filling separation buffer solution into a microchip in such a microchip processing apparatus. Also, the present invention relates to a capillary electrophoresis method for separating and analyzing samples, and a microchip processing apparatus for realizing such a capillary electrophoresis method.
In microchip electrophoresis, a sample such as DNA, RNA or protein introduced on one side of a main separation channel, is electrophoretically separated toward the other end of that channel by a voltage applied between both ends of that channel.
In microchip electrophoresis, an apparatus that automatically performs filling of buffer solution, dispensing of samples, electrophoresis, and detection of separated sample components by repeatedly using a single microchip having one electrophoresis channel has been developed (see Patent Document 1).
Electrophoresis apparatus having plural channels in order to raise operating efficiency of analysis also have been proposed. One of these apparatus has 12 channels, and after manually filling of the separation buffer solution and dispensing of the samples, it electrophoretically separates them sequentially from the 12 channels and obtains data (see Non-Patent Document 1).
Another device has 12 channels using capillaries, and it is made so as to automatically perform: filling of separation buffer solution, dispensing of samples, electrophoretic separation, and data acquisition (see Non-Patent Document 2).
In micro liquid chromatography, the microchip has a liquid delivery channel including a separation column in the form of a main channel, and separates and analyzes a sample introduced to one side of the separation column by moving it toward the other end of that separation column (see Non-Patent Document 3).    Patent Document 1: Publication of Japanese Unexamined Patent No. H10-246721    Non-Patent Document 1: “Bunseki” (“Analytical Sciences”), No. 5, pp. 267-270 (2002)    Non-Patent Document 2: Electrophoresis 2003, 24, 93-95    Non-Patent Document 3: Anal. Chem., 70, 3790 (1998)
A microchip having reservoirs opened on the surface on the respective ends of the channels is used, and the microchip is held in a manner such that the reservoirs face upward when installing on the microchip processing apparatus. At that time, when filling separation buffer solution into the channels, or when exchanging the separation buffer solution of the channels of the microchip having finished analysis, the separation buffer solution is supplied to one reservoir by a separation buffer solution filling device. The separation buffer solution is pushed into the channels by pushing an air supply port onto that reservoir and supplying air, and the separation buffer solution overflowing from the other reservoirs, is drawn off by a suction nozzle.
At this time, because it is common that the mechanism for pushing the air supply port onto the reservoir and the driving mechanism for supplying air are separate mechanisms, the apparatus tends to become bulky. Also, it is not good that the separation buffer solution which is supposed to be drawn from the reservoirs by the suction nozzle and discharged, remains in the reservoirs, and in particular when, due to repeated used of the microchip, contamination from the analytical sample of the previous time occurs and the analytical precision is lowered.
Also, in capillary electrophoresis, after the separation buffer solution is filled into the channels and the sample is injected into the channels, it is determined as to whether the phoresis operation is being performed normally or whether it will be performed normally. The method for that is a method in which the electrical current value in the sample phoresis is compared with a threshold value after starting electrophoresis of the sample, or a test current value by application of a voltage lower than the electrophoresis voltage is compared with a threshold value. In either case the normality or abnormality of phoresis is determined according to the electrified state after sample introduction. Further, the electrophoresis process is discontinued when it is determined not to be normal.
However, with the method that determines whether phoresis is normal or not after injecting the sample into the channels, because the sample submitted to analysis is already lost when it is determined not to be normal, it is difficult to measure it again in the case of a sample that can be obtained only in a small quantity.
Therefore, the first purpose of the present invention is to provide a compact and inexpensive separation buffer solution filling device by simplifying the mechanism for pushing the air supply port onto the reservoir and supplying air.
The second purpose of the present invention is to provide a separation buffer solution filling device that makes it easier to draw the separation buffer solution to be discharged from the reservoirs when filling the separation buffer solution into the channels of the microchip.
The third purpose of the present invention is to provide a microchip processing apparatus using such a separation buffer solution filling device.
The fourth purpose of the present invention is to make it such that it can be determined as to whether the filling of the separation buffer solution into the channels has been performed normally even without introducing the sample into the channels.